CASE REPORT article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1567724
This article is part of the Research TopicDNA Damage, Repair and Mutagenesis: Targeting Cancer’s Achilles HeelView all 7 articles
Response to DNA Damaging Agents and PARP Inhibitors in ATM Mutated Metastatic Colorectal Cancer: Case Series
Provisionally accepted
- Mayo Clinic Arizona, Scottsdale, United States
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The ataxia-telangiectasia mutated (ATM) gene has numerous functions, most notably related to homologous recombination and cell-cycle checkpoint activation. With increasing utilization of genetic sequencing, the prevalence of germline and somatic mutations in ATM have been more definitively established. Pathogenic ATM mutations in metastatic colorectal cancer (mCRC) are prognostically favorable, showing a median overall survival that is nearly twice as long compared to ATM wild-type cancers. The combination of DNA damaging agents coupled with interference of DNA repair mechanisms via poly (ADP-ribose) polymerase (PARP) inhibitors has also shown to be effective in patients with homologous recombination (HR) deficient malignancies. Herein, we review a series of four patients with mCRC harboring germline and somatic ATM mutations with high variant allele frequency. These cases highlight significant clinical and radiographic response to the combination of DNA damaging agents with platinum and topoisomerase inhibitor-based therapy as well as second line treatment with PARP inhibitors. There is a paucity of information in the literature with regards to PARP inhibitors in patients with mCRC. This case series may provide insight towards future investigation with this unique treatment paradigm in select patient populations containing ATM mutations or other genetic markers associated with HR deficiencies.
Keywords: Metastatic colon cancer (mCRC), ATM gene, DNA Damage, HRD (homologous recombination deficiency), PARP inhibition (PARPi), case series
Received: 28 Jan 2025; Accepted: 17 Jun 2025.
Copyright: © 2025 Eslinger, Walden, Sonbol, Ahn, Wu, Borad and Bekaii-Saab. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Cody Eslinger, Mayo Clinic Arizona, Scottsdale, United States
Tanios Bekaii-Saab, Mayo Clinic Arizona, Scottsdale, United States
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